Effector CD4+ T-cell subsets in Takayasu arteritis-differences between the peripheral blood and the aorta.

Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of six patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (P = 0.031 and P = 0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (P = 0.016 and P = 0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T-cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rho = -0.610 and rho = -0.463, respectively) and with Th17 cells (rho = -0.365 and rho = -0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet, and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.

Effect of vitamin D sterols on bone histology in pre-dialysis patients: A prospective controlled study.

BACKGROUND: Abnormalities related to mineral and bone metabolism are a common finding in chronic kidney disease (CKD). Vitamin D compounds are often prescribed to CKD patients with the purpose to control secondary hyperparathyroidism and reduce the risk of high-turnover bone disease. However, data on the effect of vitamin D sterols on bone histology in non-dialysis CKD is limited. MATERIALS AND METHODS: A prospective controlled study was conducted on a cohort of 56 patients with CKD stages 3 and 4. 19 patients on calcitriol and 12 patients on cholecalciferol were compared to a group of 25 age- and sex-matched controls. Participants underwent a tetracycline double-labelled transiliac bone biopsy before starting therapy and again 12 months later. Changes from baseline in circulating biomarkers and bone histomorphometric parameters were analyzed. RESULTS: Low-turnover bone disease was the most common pattern of renal osteodystrophy on the initial biopsy. There was no difference in biochemical or histomorphometric values between the three study groups at baseline. Serum intact parathormone (iPTH) and bone formation rate decreased significantly in calcitriol-treated patients, with prevalence of low-turnover bone disease doubling from baseline. In contrast, no significant changes were noted in cholecalciferol-treated and control subjects. CONCLUSION: Calcitriol was effective in preventing secondary hyperparathyroidism and high-turnover bone disease. However, it was associated with an increased risk of developing or aggravating low-turnover bone disease. In the absence of a bone biopsy, calcitriol use in pre-dialysis CKD should be reserved for patients with a progressive rise in iPTH levels, in whom high-turnover bone disease is suspected.

Quantitative histology as a diagnostic tool for celiac disease in children and adolescents.

OBJECTIVE: To measure the villous height, the crypt depth, and the number of intraepithelial lymphocytes/100 enterocytes of the small intestinal mucosa of children and adolescents with celiac disease; and to classify these findings according to Q- Marsh and Q-histology scales. METHODS: Retrospective study of a database from the Department of Pathology of biopsies from the second portion of the duodenum of pediatric patients. According to the histological report, three groups were established: celiac disease at diagnosis (n = 50), controls (n = 26), giardiasis (n = 10). In each biopsy, software (cellSens and Image J) evaluated 5 villous heights, 5 crypt depth and the number of intraepithelial lymphocytes/100 enterocytes. RESULTS: The celiac group had the lowest mean villous height (197.83 µm) of all three groups (control = 477.70 µm; giardiasis = 397.04 µm. The celiac group's villous:crypt ratio (0.78) was significantly lower than the control group (1.89). The number of intraepithelial lymphocytes ≥25 was exclusive to the celiac group, with a sensitivity and specificity of 100 %. Only celiac patients were included in types 2 and 3 of the Q-histology classification. CONCLUSION: Celiac disease patients showed shorter villous height than other groups, and the number of intraepithelial lymphocytes ≥25 was the best parameter to differentiate celiac from controls and giardiasis groups. Intraepithelial lymphocytes ≥25/100 enterocytes associated with any degree of villous atrophy, the classic Marsh 3 type, set the histological parameters of celiac disease. Quantitative histology is a valuable tool for diagnosing celiac disease, enabling histological changes in a short time, and the Q-histology scale appears to be more suitable than the Q-Marsh scale.

Medical students' and health professionals' knowledge regarding acute kidney injury: a cross-sectional study in the city of São Paulo, Brazil.

BACKGROUND: Acute kidney injury (AKI) is a worldwide public health problem and is often treated by non-nephrologists. The objective of this study was to evaluate the knowledge of non-nephrologists, undergraduate medical students and health professionals regarding AKI. METHODS: An unsupervised and closed-response electronic questionnaire was sent to sixth-year medical students and non-nephrologist health professionals working in the city of São Paulo, Brazil. RESULTS: A total of 424 responses were returned from 650 invitations (40.1% males, 39.2% physicians, 34.0% senior medical students or resident physicians, 16.3% nurses and 10.6% pharmacists). The knowledge of medical students and health professionals about the prevalence and lethality of AKI in hospitals ranged from 40.8% to 59.2%. The most recognized susceptibilities and risk factors for AKI were sepsis/septic shock (95.0%) and diabetes mellitus (91.3%); the less-recognized susceptibilities and risk factors were exposure to gadolinium-based contrast (23.3%) and chronic liver disease (55.7%). The study participants' rate of knowledge regarding the diagnosis of AKI was 50.9-73.6%, and their rate of knowledge regarding the criteria of increased serum creatinine and reduced urine volume was 52.6%. The most-recognized nephrotoxic medications were vancomycin (82.3%) and diclofenac (80.4%), and the least-recognized were acyclovir (34.0%) and cotrimoxazole (30.4%). The indications for emergency renal replacement therapy that were recognized by the study respondents were metabolic acidosis (82.3%), uremic syndrome (81.6%), hyperkalemia unresponsive to clinical treatment (78.1%) and acute pulmonary edema (71.6%). CONCLUSION: The study showed knowledge gaps that can impact patient care and can be used to guide professional training programs.

Economic efficiency and family income of small-scale fisheries on the north coast of São Paulo State, Brazil.

Small-scale fisheries is an important factor in the generation of income, jobs and food security. Understanding the characteristics of small-scale fisheries, and the volume of resources and food that they generate can help society recognize their value, lead to the establishment of public policies to improve working conditions and adapt the management of exploited resources for long-term conservation. The objective of this study was to estimate income, production capacity and importance of small-scale fisheries for fisher families of the municipality of Caraguatatuba, São Paulo, Brazil. Fishers were interviewed from May 2012 to June 2013 and categorized according to vessel size and the number of people on the boat and helpers. Monthly income ranged from US$ 566.78 to US$ 1,466.87. The importance of fishing to family income ranged from 50.60% (employee) to 78.25% (entrepreneur). Fishers usually dedicate themselves to this activity for 8.47 to 13.22 hours daily, with daily fish production volume ranging from 42.72 to 122.14 kg/day. Small-scale fisheries involve, either directly or indirectly, about 1,170 people in the municipality and provide a network of social protection due to their local and regional importance.

Precise, accurate and user-independent blood collection system for dried blood spot sample preparation.

An accurate and precise 3 µL blood collection and dispensing system is presented for the preparation of dried blood spot (DBS) samples. Using end-to-end glass capillaries in conjugation with pre-punched DBS pads, a blood micro collection system was developed to eliminate the haematocrit dispersion, widely associated with DBS technology, while providing better levels of accuracy and precision during sample preparation. This methodology is compared to traditional micro-volume blood collection systems, such as a pipette and a digitally controlled analytical syringe. Results showed that % of recovery for the capillary methodology was closer to 100% across the three haematocrit (HCT) levels tested and when prepared by two users (98 to 100% for capillaries, 78 to 104% for pipette and 93 to 97% for digital syringe) attesting a higher accuracy. Additionally, by taking advantage of the capillary action mechanism to collect and dispense autonomously the desired volume of blood onto the DBS pad, coefficients of variation between two individuals were significantly lower than with standard methodologies (capillaries-0.05 to 0.77%, pipette-12.71 to 18.53% and digital syringe-0.72 to 1.77%). This alternate aspiration and dispensing methodology could be used by different users without compromising accuracy or precision when handling low volumes of blood during the pre-analytical steps. Graphical abstract Comparison of novel capillary dispensing methodology for dried blood spot sample preparation with pipette and digital syringe methodologies through accuracy and precision measurements of caffeine.

Correction to: Precise, accurate and user-independent blood collection system for dried blood spot sample preparation.

The authors would like to call the reader's attention to the following: The instrument they used to measure the volumetric precision of the dispensing devices is not called "VMS" but "PCS®".

Grape juice concentrate (G8000™) modulates apoptosis but not oxidative stress following rat colon carcinogenesis induced by azoxymethane.

OBJECTIVES: The aim of this study was to evaluate if grape juice concentrate is able to protect against experimental colon carcinogenesis. MATERIAL AND METHODS: For this purpose, a total of 35 male Wistar rats were randomly distributed into seven groups: G1: SHAM animals receiving only saline; G2: animals receiving 15 mg/kg azoxymethane (AOM); G3: animals receiving 1% grape juice concentrate 2 weeks before the administration of AOM; G4: animals receiving 2% grape juice concentrate 2 weeks before the administration of AOM; G5: animals receiving 1% grape juice concentrate 4 weeks after the last administration of AOM; G6: animals receiving 2% grape juice concentrate 4 weeks after the last administration of AOM; G7: animals receiving only 2% grape juice concentrate. RESULTS: The group that received 2% grape juice concentrate before induction with AOM showed the decreased expression of Bcl-2 compared to those animals that were induced by AOM (positive control). Regarding Bax, animals that received grape juice at 2% decreased Bax immunoexpression when compared to AOM group. Furthermore, animals that intake grape juice at 1% after induced by AOM decreased Bax immunoexpression as well. 8-OHdGLI did not show significant statistically differences (p > 0.05) among groups. CONCLUSION: In summary, our results demonstrate that grape juice is able to modulate rat colon carcinogenesis as a result of induction of apoptosis.

The Effects of Enrichment on Zoo-Housed Scarlet Ibis Behavior.

Good zoo animal welfare is commonly promoted with environmental enrichment; however, some species are less likely to be offered enrichment than others. This study tested the effect of enrichment on a group of scarlet ibises from Zoomarine Algarve, Portugal. The study consisted of a first baseline condition, followed by four types of enrichment displays with individual presentations, a post-enrichment condition, and a post-enrichment with all enrichment types presented simultaneously. The enrichment types chosen were physical, with a tidal simulation in the lakes of the enclosure; nutritional, presenting mussels in a plastic mesh tube; sensory, by playing scarlet ibises calls; and tactile, with brushes through the habitat. The data collection was performed for 21 days between January and March 2021, 3 times a day, using scan sampling and instantaneous time sampling every 2 min. The comparison between conditions revealed that most behaviors showed similarity between the baseline and post-enrichment conditions, suggesting that after removing the enrichment, the behaviors returned to their initial baseline. It was also found that each enrichment influenced different types of behaviors and these behaviors also changed depending on the time of day. Exploratory behavior was only associated with the presence of enrichment, and vocalizations were only heard after the sensory enrichment was performed. This study demonstrates that the use of physical and tactile enrichments increased activity and decreased stationary behaviors in this group of ibises and may be used to improve their lives in zoological contexts if included in the housing and husbandry protocols.

The anti-inflammatory potential of phenolic compounds in grape juice concentrate (G8000™) on 2,4,6-trinitrobenzene sulphonic acid-induced colitis.

Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2% grape juice control group; 1% grape juice 24 h after TNBS colitis induction; 1% grape juice on day 7 after colitis induction; 2% grape juice 24 h after colitis induction; 2% grape juice on day 7 after colitis induction. The 1% grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1% grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (P,0·05) of TNF-a and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1% dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1% dose.

Hemophagocytic lymphohistiocytosis: a case series analysis in a pediatric hospital.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical laboratory condition with high mortality rates, resulting from ineffective overactivation of the immune system. Data in the Brazilian literature is scarce, contributing to the challenge in standardizing conducts and performing an early diagnosis of HLH. OBJECTIVE: To describe the clinical, laboratory, and evolutionary findings on HLH patients treated at a pediatric hospital. METHODS: This is an observational, cross-sectional and retrospective study on children diagnosed with HLH, hospitalized between 2009 and 2019. The diagnostic criteria were those described in the Histiocyte Society protocol. The authors evaluated HLH patient laboratory tests, myelograms and bone marrow biopsies, clinical characteristics and therapy. RESULTS: Twenty-three patients were included, 52.2% of whom were males. The age at diagnosis ranged from one to one hundred and eighty months. Four cases were classified as Primary HLH and nineteen, as Secondary HLH. The main triggers were infections and rheumatological diseases. All children had bicytopenia, and 95.4% had hyperferritinemia. Nineteen patients had liver dysfunction, sixteen had neurological disorders and fourteen had kidney injury. Pulmonary involvement was seen in 61.9%, acting as a worse prognosis for death (p = 0.01). Nine patients underwent the immuno-chemotherapy protocol proposed in the HLH 2004. The time to confirm the diagnosis varied from five to eighty days. The lethality found was 56.3%. CONCLUSIONS: The present study is the most extensive retrospective exclusively pediatric study published in Brazil to date. Despite the limitations, it was possible to demonstrate the importance of discussing HLH as a pediatric emergency.

Bilateral Gonadal Dysgerminoma in a Phenotypic Female With 46,XY Disorder of Sexual Development: A Case Report.

The 46,XY disorder of sexual development (DSD) is a rare congenital condition characterized by a 46,XY karyotype associated with complete or disturbed female gonadal development and a non-virilized phenotype. The presence of Y chromosome material in these patients' karyotypes increases the risk of germ cell tumor development. The present study reports a unique case of a 16-year-old phenotypically female patient presenting with primary amenorrhea, who was later diagnosed with 46,XY DSD. After bilateral salpingo-oophorectomy, the patient was diagnosed with stage IIIC dysgerminoma. The patient received four cycles of chemotherapy and showed a good response. The patient is currently alive and well, with no evidence of disease after the residual lymph node resection.

Hospital admission is associated with disability and late musculoskeletal pain in individuals with long COVID.

Background: The acute clinical repercussions of SARS-CoV-2 infection have been widely studied. However, the possible late repercussions of long COVID have not yet been well defined in the literature. Objectives: To identify the presence of pain and musculoskeletal disability in patients with Long COVID and also to identify predictive factors for pain intensity in this population. Methods: In this cross-sectional and retrospective observational study individuals with Long COVID symptoms were included. It was collected musculoskeletal disability measures, data from patient-related outcome measures and variables from a COVID-19 outpatient service database. Associations and sub-group analyses were performed considering the variables pain, disability and hospitalization. Linear regression was performed to identify predictive factors for pain intensity in Long COVID patients. Results: We evaluated 195 patients and most of them (57%) presented musculoskeletal pain in one area of the body. Pain sub-group presented worse disability indices and worse clinical course during hospitalization. Hospitalized patients presented worse disability indices comparing to non-hospitalized. Significant correlations were found between pain and days of non-invasive oxygen support (r = 0.21; p = 0.003); days in intensive care unit (r = 0.22; p = 0.002) and days in invasive mechanical ventilation (r = 0.35; p = 0.001). Hospitalized individuals showed a higher chance of presenting late musculoskeletal pain (OR = 1.42: 95%CI 1.09-2.04). Days in intensive care unit (ß = 0,234: P = 0,001) and days in invasive mechanical ventilation (ß = 0.764: P = 0.001) were predictors of pain intensity [F(2,192) = 18.559; R2 = 0.231; p = 0.001]. Conclusion: Individuals with Long COVID presented musculoskeletal pain and disability. Hospitalized patients showed a greater chance of having musculoskeletal pain. Days in intensive care unit and days in invasive mechanical ventilation were predictors of late musculoskeletal pain intensity.

Vascular calcification in peritoneal dialysis patients and its association with bone-derived molecules and bone histomorphometry.

INTRODUCTION: Data regarding vascular calcification (VC) in contemporary peritoneal dialysis (PD) patients is scarce. Bone-vascular axis has been demonstrated in hemodialysis (HD). However, studies showing the link between bone disease and VC in PD patients are lacking. The role of sclerostin, dickkopf-related protein 1 (DKK-1), receptor activator for nuclear factor kB ligand and osteoprotegerin (OPG) in VC in PD remains to clarify. MATERIALS AND METHODS: Bone biopsy was performed in 47 prevalent PD patients with histomorphometric analysis. Patients were submitted to pelvis and hands X-ray to evaluate VC using the Adragão score (AS). Relevant clinical and biochemical data was collected. RESULTS: Thirteen patients (27.7%) had positive AS (AS≥1). Patients with VC were significantly older (58.9 vs. 50.4 years, p=0.011), had a lower dialysis dose (KT/V 2.0 vs. 2.4, p=0.025) and a higher glycosylated hemoglobin (7.2 vs. 5.4%, p=0.001). There was not any laboratorial parameter of mineral and bone disease used in clinical practice different between patients with or without VC. All diabetic patients had VC but only 8.1% of non-diabetic had VC (p<0.001). Patients with VC showed significantly higher erythrocyte sedimentation rate (ESR) (91.1 vs. 60.0mm/h, p=0.001), sclerostin (2250.0 vs. 1745.8pg/mL, p=0.035), DKK-1 (1451.6 vs. 1042.9pg/mL, p=0.041) and OPG levels (2904.9 vs. 1518.2pg/mL, p=0.002). On multivariate analysis, only ESR remained statistically significant (OR 1.07; 95% CI 1.01-1.14; p=0.022). Bone histomorphometric findings were not different in patients with VC. There was no correlation between bone formation rate and AS (r=-0.039; p=0.796). CONCLUSION: The presence of VC was not associated with bone turnover and volume evaluated by bone histomorphometry. Inflammation and diabetes seem to play a more relevant role in VC in PD.

Fertility Does not Quarantine: Coronavirus Disease 2019 Pandemic Impacts on in Vitro Fertilization Clinical Pregnancy Rates.

OBJECTIVE: To understand the impact of the coronavirus disease 2019 pandemic on in vitro fertilization (IVF) clinical pregnancy rates and analyze factors that may have influenced their outcome. METHODS: This was a retrospective observational study conducted at a tertiary-care Brazilian fertility center. All fresh IVF and embryo warming cycles performed from March 11 to December 31, 2018-2021 were analyzed, and their data were used to calculate fertilization, embryo cleavage, cycle cancellation, embryo transfer (ET), and clinical pregnancy rates. Statistical tests were used to evaluate the alterations found. Logistic regression models were used to explore the association of the categorical variables with the observed clinical pregnancy rates. Data from 2018 and 2019 (prepandemic) and 2020 and 2021 (pandemic) were grouped. RESULTS: A total of 756 cycles were analyzed (n = 360 prepandemic and n = 396 pandemic). The age group of the patients, fertilization rates, and cleavage rates did not have significant differences (p > 0.05). There was a reduction in the percentage of fresh IVF and an increase in embryo warming cycles (p = 0.005) during the pandemic. There was also an increase in fresh cycle cancellations (p < 0.001) and a reduction in ET rates (p < 0.001). The pandemic had a negative impact on clinical pregnancy rates (p < 0.001) especially due to the increase in fresh cycle cancellations (p < 0.001). CONCLUSION: Embryo warming cycles with subsequent frozen-thawed ET were presented as a viable alternative to continue assisted reproductive treatments against pandemic restrictions on fresh cycles, ensuring clinical pregnancy, albeit at a lower rate than that of the prepandemic period.

OBJETIVO: Compreender os impactos da pandemia de COVID-19 nas taxas de gravidez clínica em fertilização in vitro (FIV) e analisar fatores que possam ter influenciado seu resultado. MéTODOS: Foi realizado um estudo observacional retrospectivo em um centro brasileiro de reprodução assistida. Todos os ciclos de FIV com embriões frescos e descongelados realizados entre 11 de março e 31 de dezembro, 2018-2021 foram analisados, e seus dados utilizados para cálculo das taxas de fertilização, clivagem embrionária, cancelamento de ciclos, transferência de embriões (TE) e gravidez clínica. Testes estatísticos avaliaram significância das alterações encontradas e modelos de regressão logística exploraram associação das variáveis categóricas estudadas com as taxas de gravidez clínica observadas. Os dados de 2018 e 2019 (pré-pandemia) e 2020 e 2021 (pandemia) foram agrupados. RESULTADOS: Foram analisados um total de 756 ciclos (n = 360 na pré-pandemia e n = 396 na pandemia). A faixa etária das pacientes e as taxas de fertilização e de clivagem não tiveram alterações significativas (p > 0,05). Na pandemia, houve redução da porcentagem de ciclos de FIV com embriões frescos e aumento dos com descongelamento (p = 0,005). Também foi notado aumento das taxas de cancelamentos de ciclos com embriões frescos (p < 0,001) e redução do número de TEs (p < 0,001). A pandemia exerceu impacto negativo na taxa de gravidez clínica (p < 0,001), especialmente devido ao aumento de cancelamentos dos ciclos a fresco (p < 0,001). CONCLUSãO: Frente às limitações pandêmicas impostas aos ciclos com embriões frescos, os ciclos de descongelamento de embriões se apresentaram como alternativa viável à continuidade dos ciclos de FIV, garantindo gravidez clínica ainda que em taxas inferiores às do período pré-pandêmico.

Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study.

BACKGROUND: Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation. METHODS: A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC. RESULTS: Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (p<0.001) and to have a higher frequency of diabetes mellitus (p = 0.017) and cardiovascular disease (p = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069), emergency room visits (p<0.001) and hospital admissions (p<0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 vs. 0.93 vs. 0.64, per patient-year; p<0.001) and hospitalizations (0.47 vs. 0.07 vs. 0.14, per patient-year; p = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (p<0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], p = 0.024). CONCLUSION: Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.

Evaluation of Renal Osteodystrophy and Serum Bone-Related Biomarkers in a Peritoneal Dialysis Population.

The spectrum of renal osteodystrophy (ROD) in peritoneal dialysis (PD) patients remains to be clarified. Ideal intact parathormone (iPTH) levels range is still not defined. The role of sclerostin, dickkopf-related protein 1, osteoprotegerin, and receptor activator for nuclear factor κB ligand for the diagnosis of ROD needs to be elucidated. In this cross-sectional study, tetracycline double-labeled bone biopsy was performed in 49 patients with histomorphometric analysis according Kidney Disease Improving Global Outcomes (KDIGO) guidelines. All patients were treated with biocompatible PD solutions, with calcium concentration of 1.25 mmol/L. Adynamic bone was the most frequent diagnosed pattern (42.9%) followed by hyperparathyroid-related bone disease (28.6%). Twenty-two percent of patients had normal bone. In patients with iPTH within the KDIGO recommended range for dialysis patients, adynamic bone was found in 59% of cases. Median (range) iPTH in patients with adynamic bone was 312 (60-631) pg/mL. Median (range) levels of sclerostin varied from 1511.64 (458.84-6387.70) pg/mL in patients with hyperparathyroid bone disease to 2433.1 (1049.59-11354.52) pg/mL in patients with adynamic bone. Sclerostin/iPTH ratio was the best marker of low turnover disease but iPTH performed best in the diagnosis of high turnover disease. Calcium mass transfer was positive in patients with low bone volume. Adynamic bone is the most frequent ROD pattern in contemporary PD. Our results suggest the need to review the iPTH target range for this population. The sclerostin/iPTH ratio showed improved performance compared to iPTH for the diagnosis of low turnover bone. © 2022 American Society for Bone and Mineral Research (ASBMR).

Could Bone Biomarkers Predict Bone Turnover after Kidney Transplantation?-A Proof-of-Concept Study.

AIM: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects of transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD). These include sclerostin and the soluble receptor activator of nuclear factor-kB ligand (sRANKL). METHODS: To better understand the role of biomarkers in post-transplant bone disease, this study was designed to prospectively evaluate and correlate results from the histomorphometric analysis of bone biopsies after KT with emerging serum biomarkers of the CKD-MBD: sclerostin, Dickkopf-related protein 1 (Dkk-1), sRANKL and osteo-protegerin (OPG). RESULTS: Our data shows a significant increase in plasma levels of bioactive sclerostin after KT accompanied by a significant reduction in plasma levels of Dkk-1, suggesting a promotion of the inhibition of bone formation by osteoblasts through the activation of these inhibitors of the Wnt signaling pathway. In addition, we found a significant increase in plasma levels of free sRANKL after KT accompanied by a significant reduction in plasma levels of its decoy receptor OPG, suggesting an enhanced bone resorption by osteoclasts mediated by this mechanism. CONCLUSIONS: Taken together, these results suggest that the loss of bone volume observed after KT could be explain mainly by the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone resorption mediated by sRANKL.

IMMUNOEXPRESSION OF DEK AND PHOSPHO-P38 PROTEINS IN RECTAL CANCER BEFORE CHEMORADIATION THERAPY.

BACKGROUND: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. OBJECTIVE: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. METHODS: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with <4 negative. RESULTS: 22 patients were included with a mean age of 63.55 years (SD: ±13.49). The clinical-stage before treatment was T3 on 72.7%, T4 on 18.2%, 31.8% were N1, 50% N0 and all M0. After chemo and radiotherapy, 54.6% were T3; 22.7% were classified as T2; 9.1% as T1, and 13.6% were T0. Among the tumors, 22.7% were positive for DEK and 63.6% positive for Phospho-P38. There was a positive correlation between DEK protein before treatment and pTNM stage (P=0.011). Phospho-P38 protein showed no correlation with these parameters. Patients with a negative HScore had a mean survival of 141.33 months (95%CI: 112.41-170.25) and those with a positive HSscore had a mean survival of 25.10 months (95%CI: 17.36-32.84; P<0.001). CONCLUSION: A higher expression of DEK was observed in advanced stages. Patients who presented DEK expression <4 had a higher survival, being a factor of worst prognosis.